Objectives - Discovery of the molecular mechanisms that underlie the deposition of calcium pyrophosphate dihydrate (CPPD) and monosodium urate (MSU) microcrystals in human articular tissues and the molecular mechanisms of the interaction between such crystals and host tissues. Procedure - A comparative study of UDPG pyrophosphorylase and yeast inorganic pyrophosphatase methods to measure plasma inorganic pyrophosphate (PPi) will be done as the results differ significantly between them. The source(s) of plasma and joint fluid PPi will be sought. Attempts to nucleate CPPD in organ cultured cartilage slices will be made. Factors affecting the solubility of CPPD and MSU microcrystals will be further defined. The species and quantities of molecules from articular cartilage, joint fluid and plasma absorbing to MSU, CPPD and other microcrystals will be studied. Further attempts to remove CPPD crystals from affected cartilage will be made.